The facilitated transfer of nucleic acids into cells is one of the most valuable and frequently used techniques of modern biological science. In today's laboratories, this technique is performed for multiple purposes, including gene therapy research, studies of gene regulation, protein structure/function analyses, as well as production of recombinant proteins. There are currently a wide variety of gene transfer methods available but each has specific shortcomings.
Nucleic acids can be delivered to cells using chemical means such as DEAE-dextran-Diethylaminoethyl-dextran (DEAE-Dextran), calcium phosphate precipitation, cationic lipids (lipofection), polyethylenimine (PEI), and with targeting proteins and peptides in combination with cationic lipids. Unfortunately, there are a limited range of cell types in which DEAE-dextran works effectively. The calcium phosphate method is sensitive to slight changes in buffer salt concentrations, temperature, and pH, and has relatively poor transfection efficiency compared to newer transfection methods, especially in suspension cells such as lymphocytes. With regard to cationic lipids, several types of primary cultured cells, such as primary neurons, primary dendritic cells, and primary endothelial cells remain recalcitrant to non-viral mediated transfection methods, including cationic lipids. Moreover, the application of cationic lipid to in vivo gene delivery remains difficult.
Existing targeting proteins are typically used in combination with cationic lipids. For example protamine sulfate with DNA followed by addition of cationic lipids has been reported to enhance transgene expression in cultured cells compared to DNA delivery with lipids alone. Unfortunately, certain viral targeting proteins can cause immunogenic responses in hosts. Additionally, the interaction of cationic lipids with serum proteins can significantly reduce the efficiency of transfection.
It is an object of the invention to provide synthetic compositions containing lipid rafts and methods of use thereof for delivering cargo to cells.
It is still another object of the invention to provide methods for treating a disease, disorder, or a symptom of a disease or disorder using synthetic compositions containing lipid rafts.
It is yet another object of the invention to provide synthetic compositions containing lipid rafts for transfecting cells in vitro or in vivo.
It is another object to provide methods and compositions for identifying modulators of vesicular traffic.